Medicinal Chemistry Research Laboratory, School of Chemical Sciences, Solapur University, Solapur 413 255, Maharashtra, India.
Bioorg Med Chem Lett. 2013 Mar 1;23(5):1315-21. doi: 10.1016/j.bmcl.2012.12.094. Epub 2013 Jan 9.
A series of novel pyrazole amalgamated flavones has been designed and synthesized from 1-methyl-5-(2,4,6-trimethoxy-phenyl)-1H-pyrazole 6. The structures of regioisomers 6 and 7 were resolved by 2D (1)H-(1)H COSY, (1)H-(13)C HSQC and (1)H-(13)C HMBC experiments. The newly synthesized compounds were tested for their in vitro COX inhibition and in vivo carrageenan induced hind paw edema in rats and acetic acid induced vascular permeability in mice. Although the compounds have inhibitory profile against both COX-1 and COX-2, some of the compounds are found to be selective against COX-2, supported by inhibition of paw edema and vascular permeability. Docking studies were also carried out to determine the structural features which sway the anti-inflammatory activity of the tested compounds. The keto and phenolic -OH are major factors that are prominently involved in interaction with COX-2 active site.
从 1-甲基-5-(2,4,6-三甲氧基苯基)-1H-吡唑 6 设计和合成了一系列新型吡唑稠合的黄酮类化合物。通过 2D(1)H-(1)H COSY、(1)H-(13)C HSQC 和(1)H-(13)C HMBC 实验解析了区域异构体 6 和 7 的结构。对新合成的化合物进行了体外 COX 抑制活性以及体内角叉菜胶诱导的大鼠后爪水肿和醋酸诱导的小鼠血管通透性的测试。尽管这些化合物对 COX-1 和 COX-2 均有抑制作用，但一些化合物对 COX-2 具有选择性，这得到了抑制后爪水肿和血管通透性的支持。还进行了对接研究以确定影响测试化合物抗炎活性的结构特征。酮和酚-OH 是主要与 COX-2 活性位点相互作用的因素。
